Ethyl Acetate → 4-n-Butyl-1-[4-(2-benzyloxyphenyl)-4-oxo-1-butyl]piperidine

HRID 1859635Notes

Reaction equation

HRID 1859635 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1I)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:16]([CH:20]1[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][CH2:28][C:29]#N)[CH2:22][CH2:21]1)[CH2:17][CH2:18][CH3:19].CC[O:33]C(C)=O>CCOCC.C(Cl)Cl>[CH2:16]([CH:20]1[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][CH2:28][C:29]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:33])[CH2:22][CH2:21]1)[CH2:17][CH2:18][CH3:19]

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 119842101-(Benzyloxy)-2-iodobenzeneHCID 186263854-(4-Butylpiperidin-1-YL)butanenitrile

Product 1

HCID 186263744-n-Butyl-1-[4-(2-benzyloxyphenyl)-4-oxo-1-butyl]piperidineYield 51%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

In a 25 mL oven-dried flask was added Mg turnings (123 mg, 5.1 mmol) which was activated by the use of a heat-gun under vacuum. Under inert atmosphere was added a solution of 1-benzyloxy-2-iodo-benzene (25) (1.18 g, 3.8 mmol) in Et2O (10 mL) and the reaction mixture was allowed to reflux for 3.5 hours. A solution of 4-(4-n-butylpiperidin-1-yl)butanenitrile 4 (0.53 g, 2.5 mmol) dissolved in CH2Cl2 (3 mL) was added and the reaction mixture and was stirred at 40° C. over-night. The reaction mixture was quenched by addition of H2SO4 (10 mL, 2 M) and left stirring for 1 hour, followed by addition of NaOH (20 mL, 2 M) until basic conditions. The reaction mixture was extrated with ethyl acetate (3×50 mL)) and the combined organic phases are washed with brine (10 mL) and NaOH (10 mL, 2 M), and the combined organic phases were dried (MgSO4) and evaporated to dryness to produce 1.28 g of crude 26. The crude product was subjected to CC [eluent: Tol:EtOAc (1:1)] to give pure 26 (0.51 g, 51%); LC-MS [M+H]+ 393 (cald. 393.7).

Workup

  1. customIn a 25 mL oven-dried flask
  2. temperaturea heat-gun under vacuum
  3. temperatureto reflux for 3.5 hours
  4. additionwas added
  5. customThe reaction mixture was quenched by addition of H2SO4 (10 mL, 2 M)
  6. waitleft
  7. stirringstirring for 1 hour
  8. additionfollowed by addition of NaOH (20 mL, 2 M) until basic conditions
  9. washare washed with brine (10 mL) and NaOH (10 mL, 2 M)
  10. dry with materialthe combined organic phases were dried (MgSO4)
  11. customevaporated to dryness
  12. customto produce 1.28 g of crude 26

Sources & evidence

ORD record
ord-a57b014fdb5a467c80c52e958d354099
Source dataset
uspto-grants-2003_03
Patent number
US06528529B1

Reaction notes

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